Pharmacovigilance

PharmaWiz

Mr. PharmaWiz 11/24/21 Interview Q&A

Define Pharmacovigilance:

Pharmacovigilance, also known as drug safety, is the pharmacological science

relating to the collection, detection, assessment, monitoring, and prevention of
adverse effects with pharmaceutical products.

The etymological roots for the word "pharmacovigilance" are: pharmakon (Greek
for drug) and vigilare (Latin for to keep watch). As such, pharmacovigilance
heavily focuses on adverse drug reactions (ADR).

Recently, its concerns have been widened to include:

• herbals
• traditional and complementary medicines
• blood products
• biologicals
• medical devices and vaccines.

Good Clinical Practice (GCP): International ethical and scientific quality standard
for designing, conducting, monitoring, recording, auditing, analyzing and
reporting studies. Ensures that the data reported is credible and accurate, and
that subject's rights and confidentiality are protected.

ICH: The International Council on Harmonization of Technical Requirements for

the Registration of Pharmaceuticals.

WHO DD: World Health Organization Drug Dictionary.

Pharmacology: Study of the uses, effects and modes of action of drugs.

Adverse event:

Any untoward medical occurrence in a patient or clinical investigation subject

administered a pharmaceutical product and which does not necessarily have to
have a causal relationship with this treatment.

Adverse drug reaction:

Any noxious and unintended response to a medicinal product which occur at any
dose which has a casual association with the suspect drug.

Side effect:

Any unintended effect of pharmaceutical products occurred/appeared at normal

dosage used in humans, which is related to the pharmacological properties of the
drugs.

Unintended effect occurring at normal dose related to the pharmacological action

of drug.

Drug: As defined by the Food, Drug and Cosmetic Act, drugs are "articles (other
than food) intended for the use in the diagnosis, cure, mitigation, treatment, or
prevention of disease in Humans or other animals, or to affect the structure or
any function of the body of Humans or other animals."
Generic Drug: A medicinal product with the same active ingredient, but not
necessarily the same inactive ingredients as a brand name drug. A generic drug
may only be marketed after the original drug's patent has expired.

Placebo: An inactive substance designed to resemble the drug being tested. It is

used as a control to rule out any psychological effects testing may present. Most
well-designed studies include a control group which is unwittingly taking a
placebo

Regulatory Bodies: The legal authority in any country with the responsibility of
regulating all matters relating to drugs.

USA: United States Food and drug administration (USFDA).

Europe: European Medicines Agency (EMEA).

Japan: Ministry of Health, Labor, and Welfare (MHLW).

India: Central Drugs Standard Control Organization (CDSCO)

Health Canada

UK: The Medicines and Healthcare products Regulatory Agency.

TGA: The Therapeutic Goods Administration

Medication Error: Medication errors are mishaps that occur during prescribing,
transcribing, dispensing, administering, adherence, or monitoring a drug.
Examples of medication errors include misreading or miswriting a prescription.

Drug Abuse: This corresponds to the persistent or sporadic, intentional excessive

use of a medicine, which is accompanied by harmful physical or psychological
effects.
Signal: Signal is a possible causal relationship between adverse event and drug,
previously unknown or incompletely documented.

Causality: The relationship between administration of a drug (cause) and an

adverse event (effect)

Causality assessment is the evaluation of the likelihood that a medicine was the
causative agent of an observed adverse reaction.

Causality assessment is usually made according established algorithms.

Causality Assessment Criteria:

The association in time between drug administration and event.

Pharmacology (features, previous knowledge of side effects)

Medical plausibility (characteristic signs and symptoms, laboratory tests,

pathological findings)

Likelihood or exclusion of other causes.

Temporal Relationship: Temporal relationship is considered positive, if the

adverse event occurring during the course of suspect drug intake or before drug
withdrawal from body.

Causality Assessment Methods:

World Health Organization Scale.

Naranjo Scale.

French Imputability Method.

Karch and Lasagna.

Binary Method.

Serious Adverse Event: Any adverse event that could result in following

Results in death.

Life threatening.

Results in inpatient hospitalization or prolongation of existing hospitalization.

Results in a persistent or significant disability/incapacity.

Results in a congenital anomaly/birth defect.

Other medically significant Events (Based upon appropriate medical judgment,

may jeopardize the subject’s health and may require medical or surgical
intervention to prevent one of the other outcomes listed)

All events listed in IME (Important Medical Event) list by EudraVigilance are
considered serious.

By referring grades of CTCAE (Common Terminology Criteria for Adverse Event).

Grade 1- Mild

Grade 2- Moderate

Grade 3- Severe

Grade 4-Life threatening

Grade 5- Fatal or Death.

Absolute risk: The probability of an event affecting members of a particular
population (e.g., 1 in 1,000). Absolute risk can be measured over time (incidence)
or at a given time (prevalence). Also, see Attributable risk and Relative risk.

Benefit: An estimated gain for individual or a population, also see

Effectiveness/Risk.

Disease: A disease is a particular abnormal condition that negatively affects the

structure or function of all or part of an organism, and that is not due to any
immediate external injury. Diseases are often known to be medical conditions
that are associated with specific signs and symptoms.

Sign: Any objective evidence of disease, as opposed to a symptom, which is, by

nature, subjective. For example, gross blood in the stool is a sign of disease; it is
evidence that can be recognized by the patient, physician, nurse, or someone
else.

Symptoms: A physical or mental problem that a person experiences that may

indicate a disease or condition. Symptoms cannot be seen and do not show up on
medical tests. A symptom is something felt or experienced.

Case Report Form (CRF): A record of pertinent information collected on each

subject during a clinical trial, as outlined in the study protocol.
Health Care Professional: A “physician or other qualified health care
professional” is an individual who is qualified by education, training,
licensure/regulation (when applicable). Example: Physician, pharmacist, Nurse or
any other qualified personal.

Clinical trials are research studies performed in people that are aimed at
evaluating a medical, surgical, or behavioral intervention. They are the primary
way that researchers find out if a new treatment, like a new drug or diet or
medical device both safe and effective.

A clinical trial could involve

new drugs, medical devices, biologicals, vaccines,
surgical and other medical treatments and procedures. Psycho-therapeutic and
behavioral therapies help service changes, preventative care strategies and
educational interventions are also examples of clinical trials.

Phase 0- Human micro dosing studies/Pre clinical or Laboratory Studies

(To Study Toxicity of New molecule).

Phase 1- Human pharmacology trails (Safety and Posology)

Phase 2- Therapeutic exploratory trials (Safety and Efficacy)

Phase 3- Therapeutic confirmatory trails (Safety, Efficacy, Comparative

studies, psychological studies, Blinded Studies and Approval of Drug for
marketing)

Phase 4- Post Marketing Surveillance.

Investigational New Drug Application (IND): The petition through which a drug
sponsor requests the FDA to allow human testing of its drug product.
New Drug Application (NDA): The compilation of all non-clinical, clinical,
pharmacological, and pharmacokinetic and stability information required about a
drug by the FDA in order to approve the drug for marketing in the U.S.

International Birth Date (IBD): When the drug got approved by FDA for
marketing, the approved date called as IBD.

Orphan Drug: A designation of the FDA to indicate a therapy developed to treat a

rare disease (one which afflicts a U.S. population of fewer than 200,000 people).
Because there are few financial incentives for drug companies to develop
therapies for diseases that afflict so few people, the U.S. government offers
additional incentives to drug companies to develop these drugs.

Over-the-Counter (OTC): Drugs available for purchase without a physician's

prescription.

CIOMS: The Council for International Organizations of Medical Sciences. CIOMS is

a body set up under World Health Organization and UNESCO. It has developed a
series of guidelines on pharmacovigilance, drawn up by a committee of volunteers
from Industry, regulatory authorities, WHO and others.

Medication error: This is an unintended failure in the drug treatment process that
leads to, or has the potential to lead to harm to the patient.

Prescription only medicine (POM): Medicinal product available to the public only
on prescription.
PSUR: The Periodic Safety Update Report (PSUR) is a stand-alone document that
allows a periodic but comprehensive assessment of the worldwide safety data of
a marketed drug or biological product.

UMC: the Uppsala Monitoring Centre.

WHO: World Health Organization.

ICSR: Individual Case Safety Report.

Biological products: Medical products prepared from biological material of

human, animal or microbiologic. Example: Vaccines and insulin.

Individual Case Safety Report (ICSR): A report that contains ‘information

describing a suspected adverse drug reaction related to the administration of one
or more medicinal products to an individual patient’.

Pharmacoepidemiology: Study of the use and effects of drugs in large

populations.

Phocomelia: Characteristic deformity caused by exposure to thalidomide in the

womb, also very rarely occurring spontaneously. Meaning: limbs like a seal.

Post-marketing: The stage when a drug is generally available on the market.

Spontaneous reporting System: whereby case reports of adverse drug events are
voluntarily submitted from health professionals and pharmaceutical
manufacturers to the national regulatory authority.

Thalidomide: Drug prescribed in the 1950s as a mild sleeping pill and remedy for
morning sickness for pregnant women. Led to serious birth defects and the start
of modern pharmacovigilance. Returning to favor in treatment of serious diseases
such as cancer and leprosy.

WHO Drug Dictionary (WHO DD): The WHO Drug Dictionary is an international
classification of drugs providing proprietary and non-proprietary names of
medicinal products used in different countries, together with all active
ingredients.

Misuse: This refers to situations where the medicine is intentionally and

inappropriately used not in accordance with the authorized Product information
or the directions for use on the medicine label.

Vaccine pharmacovigilance: is defined as the science and activities relating to

the detection, assessment, understanding, prevention, and communication of
adverse events following immunization, or of any other vaccine- or immunization-
related issues.

Covid-19 Vaccines:

Moderna. mRNA-1273. Phase 1

Pfizer/BioNTech. BNT162b2 and Comirnaty.
Janssen (Johnson & Johnson) Ad26.COV2. S. Phase 1
Oxford/AstraZeneca. AZD1222
Serum Institute of India. Covishield (Oxford/AstraZeneca formulation)
Bharat Biotech. Covaxin.
Sinopharm (Beijing) BBIBP-CorV (Vero Cells) ...
Sinovac. CoronaVac.
Sputnik V.
MEDDRA (Medical Dictionary for Regulatory Activities, Version: 24.1):

Med DRA is developed by ICH and maintained by MSSO.

Med DRA is used to code medical conditions such as Adverse events, therapeutic
indication, medical history and laboratory data in Safety Database.

Med DRA gets updated twice in a year. Major update in the month of March and
Minor update in the month of September.

Hierarchy in MedDRA:

System organic class (SOC)

High Level Group Term (HLGT)

High level Term (HLT)

Preferred Term (PT)

Lower-Level Term (LLT).

ICH was created in 1990 and is defined as International Council for Harmonization
of Technical Requirements for Pharmaceuticals for Human Use.

Harmonization of technical requirements.

Ensure safety, efficacy and quality of medicines.

Prevent duplication of clinical trials in humans.

Minimize the use of animal testing without compromising safety and

effectiveness
Quality Guidelines (Q1 to Q14): Relating to chemical and pharmaceutical.
QA (e.g., Stability testing, impurity testing, GMP)

Safety Guidelines (S1 to S12): Relating to in vitro and in vivo pre-clinical studies
(e.g., carcinogenicity, genotoxicity, toxicity testing etc.).

Efficacy guidelines (E1 to E20): Relating clinical study in human subjects (Dose
response study, Pharmacovigilance activities, case report study GCP)

Multi-disciplinary Guidelines (M1 to M12): Topics that do not fit in above

category are included in this section (e.g., MedDRA, ESTRI etc..).

Pharmacovigilance related ICH guidelines:

E2A-Reporting on safety in clinical trials.

E2B- Electronic reporting of adverse events.

E2C- Periodic safety update reports.

E2D- Reporting on safety – post marketing.

E2E- Pharmacovigilance planning.

E2F- Development safety update reports.

M1- MedDRA terminology.

M2- Electronic standard for the transfer of regulatory information

(ESTRI).

M5- Data Elements and standards for Drug Dictionaries.

Sources of Individual Case Safety Reports:

A spontaneous report is an unsolicited communication or voluntary reporting of

adverse events after intake of pharmaceutical product by a healthcare
professional or consumer to a company, Regulatory authority or other
organization.

Literature Reports: Cases of ADRs from the scientific and medical literature,
including relevant published abstracts from meetings and draft manuscripts,
might qualify for expedited reporting.

Each MAH is expected to regularly screen the worldwide scientific literature by

accessing widely used systematic literature reviews or reference databases.

Internet Reports: ADR reports from Internet, social media and Websites.

Other Sources: ADR information from non-medical source such as Lay press or
other media should be handled as spontaneous reports.

Solicited Reports or Study Reports: Solicited reports are those derived from
organized data collection systems.

E.g.: registries, post-approval named patient use programs, other patient support
and disease management programs, surveys of patients or healthcare providers,
or information gathering on efficacy or patient compliance.

Contractual Agreements: The licensing /contractual agreements should specify

the processes for exchange of safety information, including timelines and
regulatory reporting responsibilities.
Regulatory Authority Reports: Individual serious unexpected adverse drug
reaction reports originating from foreign regulatory authorities are subject to
expedited reporting to other authorities by each MAH.

Good Pharmacovigilance Practices (GVP): GVP are the set of measures drawn up
to facilitate the performance of pharmacovigilance in Europe Region.

Module I: Pharmacovigilance systems and their quality systems.

Module II: Pharmacovigilance system master file
Module III: Pharmacovigilance inspections
Module IV: Pharmacovigilance audits
Module V: Risk Management Systems
Module VI: Management and reporting of adverse reactions to medicinal
products.

Module VII: Periodic safety update report

Module VIII: Post-authorization safety studies

Module VIII: Addendum I - Member States' requirements for transmission of

information on non-interventional post authorization safety studies.

Module IX: Signal management

Module X: Additional monitoring

Module XV: Safety communication.

Module XVI: Risk minimization measures Selection of tools and effectiveness

indicators.

Module XVI: Addendum I – Educational materials.

GVP Module VI: Collection, management and submission of reports of suspected
adverse reactions to medicinal products.

This Module of GVP addresses the collection, data management and submission
of individual reports of suspected adverse reactions (serious and non-serious)
associated with medicinal products for human use authorized in the European
Union (EU).

The guidance does not address the collection, management and submission of
individual reports of events or patterns of use, which do not result in suspected
adverse reactions (e.g., asymptomatic overdose, abuse, misuse or medication
error) and which are not required to be submitted as individual case safety
reports (ICSRs).

Drug Labelling: Drug labelling refers to all printed information that accompanies a
drug including the label and packaging insert.

Labelling applies to prescription of drugs, OTC (over the counter) medications and
dietary Supplements.

Reference Safety Information contains all relevant safety information prepared

by MAH (Marketing Authorization Holder) which requires to be listed in all
countries where the drug is marketed.

Company Core Data Sheet (CCDS)

Company Core Safety Information (CCSI)
Investigators Brochure (IB)
Abbreviated Prescribing information
Summary of Product Characteristics (SPC)
Patient information leaflet (PIL)
United States Package Insert (USPI) and Japan Package Insert (JPI).
Regulatory (Submission) Timelines of ICSR:
Death or Life threatening (7 Calendar days).
Serious cases (15 Calendar days).
Non-Serious cases (90 days for ROW and 30 days for US).

Action taken: Decision made with respect to drug in response to event.

De-challenge: Drug withdrawn, temporarily hold or Dose reduction in response to

event.
Positive- Drug withdrawn adverse event diminished.

Negative- Drug withdrawn adverse event remains the same or increased

Unknown- Drug withdrawn but we don’t know the result of de

challenge NA- Drug has not stopped/ not withdrawn.
Re-challenge: Re administration of drug after recovery of an event.

Positive- Drug re introduced and event re appeared

Negative- Drug re introduced event did not re appeared

Unknown- Drug re introduced but don’t know whether the event re
appeared or not NA- Drug has not re-introduced again.

What is the minimum criterion required for a valid case according to WHO?

a. An identifiable reporter

b. An identifiable patient

c. A suspect product

d. An adverse drug event.

What should a narrative consist of?

A narrative should consist of precise and concise information about the source of
report, patient demographics, patient’s medical history, concomitant
medications, suspect product details and adverse event details in an orderly
manner.

Absolute risk: The probability of an event affecting members of a particular

population (e.g., 1 in 1,000). Absolute risk can be measured over time (incidence)
or at a given time (prevalence). Also, see Attributable risk and Relative risk.

Benefit: An estimated gain for individual or a population, also see

Effectiveness/Risk.

Disease: A disease is a particular abnormal condition that negatively affects the

structure or function of all or part of an organism, and that is not due to any
immediate external injury. Diseases are often known to be medical conditions
that are associated with specific signs and symptoms.

Sign: Any objective evidence of disease, as opposed to a symptom, which is, by

nature, subjective. For example, gross blood in the stool is a sign of disease; it is
evidence that can be recognized by the patient, physician, nurse, or someone
else.

Symptoms: A physical or mental problem that a person experiences that may

indicate a disease or condition. Symptoms cannot be seen and do not show up on
medical tests. A symptom is something felt or experienced.
Case Report Form (CRF): A record of pertinent information collected on each
subject during a clinical trial, as outlined in the study protocol.

International Birth Date (IBD): When the drug got approved by FDA for
marketing, the approved date called as IBD.

Individual Case Safety Report (ICSR): A report that contains ‘information

describing a suspected adverse drug reaction related to the administration of one
or more medicinal products to an individual patient’.

Pharmacoepidemiology: Study of the use and effects of drugs in large

populations.

Phocomelia: Characteristic deformity caused by exposure to thalidomide in the

womb, also very rarely occurring spontaneously. Meaning: limbs like a seal.

Post-marketing: The stage when a drug is generally available on the market.

Thalidomide: Drug prescribed in the 1950s as a mild sleeping pill and remedy for
morning sickness for pregnant women. Led to serious birth defects and the start
of modern pharmacovigilance. Returning to favor in treatment of serious diseases
such as cancer and leprosy.
Medical Device Reporting (MDR) is one of the post market surveillance tools the
FDA uses to monitor device performance, detect potential device-related safety
issues, and contribute to benefit-risk assessments of these products.

Drug/medicine: Any substance in a pharmaceutical product that is used to modify

or explore physiological systems or pathological states for the benefit of the
recipient. The term drug/medicinal product is used in a wider sense to include
the whole formulated and registered product, including the presentation and
packaging, and the accompanying information.

Medical Device Pharmacovigilance is the monitoring of safety profiles of medical

devices, from the processing and reporting of single adverse incidents through the
removal of products from the market as part of Field Safety Corrective action. This
is to ensure that patients and health care professional’s safety is monitored and
action taken as soon as a safety concern with medical device issues.

Medical device vigilance, as known as materiovigilance, is the collection,

assessment, reporting and identification of trends in incidents resulting from the
use of medical devices. Its primary purpose is to protect and improve safeguards
for patients, users and others by preventing or reducing the likelihood of
reoccurrence of incidents elsewhere.

Manufacturers of medical devices are subject to regulatory controls overseen by

national regulatory authorities (RA's). The RA specifies procedures to be followed
by manufacturers during the design, manufacture, and marketing of each device,
and describes the manner in which a manufacturer should demonstrate
conformity to such procedures.
The determination of class is based on rules derived from the potential of a
medical device to cause harm to a patient or user (i.e., the hazard it presents) and
thereby on its intended use and the technologies it utilizes.

Global Harmonization Task Force (GHTF) has prepared guidance document with
set of rules which assist a manufacturer to allocate its medical device to an
appropriate class using a set of classification rules; and allow RAs to pronounce
upon matters of interpretation for a particular medical device, when required so
to do.

General classification system for medical devices as per Global Harmonization

Task Force (GHTF):

• Class A: Low hazard (ex: Bandages/tongue depressors)

• Class B: Low moderate hazard (ex: hypodermic needles/suction equipment)
• Class C: Moderate to high hazard (ex: Lung ventilator / bone fixation plate)
• Class D: High Hazard (Heart valves / implantable defibrillator).

MEDICAL DEVICE REGULATORY CLASSIFICATION IN THE U.S:

In the United States, medical devices are regulated by the Food & Drug
Administration, or FDA. The specific branch within the FDA is the Center for
Devices & Radiological Health (CORN).
The mission of CDRH is to protect and promote public health. In the U.S., medical
devices are either Class I, Class II, or Class III. The FDA CDRH classification is based
primarily on risk the medical device poses.

Classification is directly related to intended use and indications for use.

• Intended Use is the general purpose of the medical device or its Function (what
you “claim" the medical device does).
• Indications for Use describe the disease or condition the medical device will
diagnose, treat, prevent, cure, or mitigate, including a description of the target
patient population.

FDA defines three regulatory controls for each medical device class:

• Class I medical device (low to moderate risk): General Controls

• Class II medical device (moderate to high risk): General Controls and Special
Controls
• Class III medical device (high risk): General Controls and Premarket Approval
(DMA).

Medical Device Reporting Timelines:

Once the company became aware of reportable incident the clock starts. If a
death or serious injury has occurred it has to be reported between 2 and 10
calendar days (refer below table). Less serious events/incidents can be reported
in 15 to 30 calendar days. If there is an incident but unsure if it is reportable,
submit a report anyway. It's important to remember that filing a report on an
incident/event is not an admission of either liability or that device caused or
contributed to the event. When in doubt, report.

File a report with a medical device Regulatory Authority when:

• A death or serious deterioration of health has occurred.

• A serious public health threat has emerged.

• A sustained negative trend has developed.

• A recall or field safety corrective action (FSCA) has been issued.

Generally, if labeling is sufficient, reporting is not required when:

• There is a very small likelihood of death or serious injury.

• The incident was caused by patient/user error.
• The service life or shelf life of the device was exceeded.
• The side effects were predictable and disclosed.
• A device problem was discovered by the user prior to use.
• The device shutoff or fault mechanism worked as designed.
FDA-Medical Device Safety Reporting:

As per FDA - MDR regulation, manufacturers are required to report to the FDA
when they learn about MDR reportable events (that one of their devices may
have caused or contributed to a death or serious injury or has malfunctioned and
this device or similar device would be likely to cause or contribute to a death or
serious injury, if the malfunction were to reoccur).

Reporting requirements: Manufacturers of medical devices are required to

submit reports to FDA of a reportable death, serious injury, or device malfunction.
A reportable death, serious injury, or malfunction is based on information a
manufacturer receives or otherwise becomes aware of, from any source, which
reasonably suggests that one of its marketed devices:

• May have caused or contributed to a death or serious injury;

• Malfunctioned and the malfunction of the device or a similar device marketed

by the manufacturer would be likely to cause or contribute to a death or serious
injury if the malfunction were to recur.
 General Interview Question’s
Tell me about yourself or brief us about yourself?

Start from your name, your native, your family member, brief note on what your
parent's occupation.

Details about where you did your schooling and other educational details.

Brief introduction of your achievements in school or college life.

In case you are a post graduate, then give a brief introduction of your project
during Masters and then little about your social life like your hobbies and other
things.

Tips:

Introduction is asked just to see how well you present about yourself.

Be Precise and Specific about what you speak.

Be optimistic and highlight all positive things.

Why you want to Join our company and why Pharmacovigilance:

Be Diplomatic, say that heard a lot of good things like work culture about the
company through Senior, or relative associated with company.

Tell, it is one of the leading MNCs and always been looking for such a platform to
start your career.
What will you do if you get a better opportunity in some other company in
terms of designation or salary:

I have been always dreaming to start career with a reputed company where I can
learn new skill and gain knowledge. If I am, selected ..this would be my first job
and I would like to stick though I receive a better offer from a different company.

How much Salary do u expect:

As a fresher, I am looking forward to start career with a reputed company and an

opportunity is what matters. Therefore, I would be happy with salary as per
company standards.

Would you prefer to relocate to office location:

Sure, I have been always looking to travel new places and know new culture. if
opportunity given ..i would be happy to relocate to work location.

How do you know about Pharmacovigilance:

PCI has included pharmacovigilance as an optional subject in curriculum of final

year (graduation). I have been taught by my professors at college and also known
about pharmacovigilance as a good career option from my seniors who are
working in the industry. I have developed interest and learnt from google and
YouTube videos.

Would you prefer to work in shifts as per requirement:

Sure, I don’t have any problem to work in shifts as per requirement.